A Study to Assess the Levels of CAZ-AVI and Metronidazole in the Blood When Given Together and Separately

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01534247

Collaborator

Forest Laboratories (Industry)

Enrollment

Location

Arms

Duration (Months)

5.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to assess whether there is any pharmacokinetic interactions between CAZ-AVI and metronidazole.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: CAZ-AVI Drug: metronidazole Drug: CAZ-AVI + metronidazole	Phase 1

Detailed Description

A Phase I, Open-Label, 3-way Crossover, Pharmacokinetic and Drug-Drug Interaction Study of ceftazidime avibactam (CAZ-AVI) and Metronidazole when Administered Alone and in Combination in Healthy Subjects

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Phase I, Open-Label, 3-way Crossover, Pharmacokinetic and Drug-Drug Interaction Study of Ceftazidime Avibactam (CAZ-AVI) and Metronidazole When Administered Alone and in Combination in Healthy Subjects

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CAZAVI CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	Drug: CAZ-AVI Infusion
Active Comparator: Metronidazole Metronidazole (500 mg)	Drug: metronidazole Infusion
Active Comparator: CAZAVI+metronidazole CAZ-AVI (2000mg ceftazidime/500 mg avibactam) + metronidazole (500 mg)	Drug: CAZ-AVI + metronidazole Infusion

Arm

Intervention/Treatment

Experimental: CAZAVI

CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)

Drug: CAZ-AVI

Infusion

Active Comparator: Metronidazole

Metronidazole (500 mg)

Drug: metronidazole

Infusion

Active Comparator: CAZAVI+metronidazole

CAZ-AVI (2000mg ceftazidime/500 mg avibactam) + metronidazole (500 mg)

Drug: CAZ-AVI + metronidazole

Infusion

Outcome Measures

Primary Outcome Measures

Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components [CAZ-AVI: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.5, 2.75, 3, 4, 5, 7, 11, 23, 73, 73.5, 74, 74.5, 75, 75.25, 75.5, 75.75, 76, 77, 78, 80, 84 and 95 hours post-dose]
Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components [Metronidazole: pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 72, 72.5, 73, 73.25, 73.5, 74, 75, 76, 78, 80, 84 and 96 hours post-dose]
Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components [CAZ-AVI and metronidazole: pre-dose, 0.5, 1, 1.25, 1.5, 2.5, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 24, 72, 72.5, 73, 73.25, 73.5, 74, 74.5, 75, 75.25, 75.5, 75.75, 76, 77, 78, 80, 84 and 96 hours post-dose]

Secondary Outcome Measures

To assess safety and tolerability of CAZ-AVI and metronidazole when administered as a 2- and 1-hour infusion, respectively, every 8 hours by assessment of adverse events, lab, vital signs, ECG, physical examination [Screening up to 26 days after first dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Provision of signed and dated, written informed consent prior to any study-specific procedures.
Healthy male and female subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture; female subjects must be post menopausal or surgically sterile.
Male subjects should be willing to use barrier contraception ie, condoms, from the first day of the investigational product administration until 3 months after the last administration of the investigational product.
Have a body mass index (BMI) between 19 and 30 kg/m2
Be able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the Investigator

Exclusion Criteria:

History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
Known history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to carbapenem or cephalosporin antibiotics or other beta-actam antibiotics or any other investigational product to be administered as part of the study
Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks prior to the first administration of investigational product Any clinically significant abnormalities in physical examination, ECG, clinical chemistry, haematology, or urinalysis results, as judged by the Investigator